ABSTRACT: Some commensal bacteria stimulate the immune system but do not present specific antigenicity. Such adjuvant effects have been reported for the bacterial species Lactobacillus plantarum. To study in vivo human responses to L. plantarum, a randomised double-blind placebo-controlled cross-over study was performed. Healthy adults were provided preparations of living and heat-killed L. plantarum bacteria, biopsies were taken from the intestinal mucosa and altered transcriptional profiles were analysed. Transcriptional profiles of human epithelia displayed striking differences upon exposure to living L. plantarum bacteria harvested at different growth phases. Modulation of NF-κB-dependent pathways was central among the major altered cellular responses. This unique in vivo study shows which cellular pathways are associated with the induction of immune tolerance in mucosal tissues towards common adjuvanticity possessing lactobacilli. Keywords: mucosal response of healthy adult humans to lactic acid bacteria This study was set up according to a randomised double-blind cross-over placebo-controlled design. It contains transcriptional profiles from biopsies from 8 healthy individuals after oral intake of three different growth stages of Lactobacillus plantarum or placebo control. In total, this study includes data from 8 individuals x 4 treatments=32 arrays.

Proceedings of the National Academy of Sciences of the United States of America 20090203 7

How do we acquire immune tolerance against food microorganisms and commensal bacteria that constitute the intestinal microbiota? We investigated this by stimulating the immune system of adults with commensal Lactobacillus plantarum bacteria. We studied the in vivo human responses to L. plantarum in a randomized double-blind placebo-controlled cross-over study. Healthy adults ingested preparations of living and heat-killed L. plantarum bacteria. Biopsies were taken from the intestinal duodenal mu ...[more]

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Project description:Some commensal bacteria stimulate the immune system but do not present specific antigenicity. Such adjuvant effects have been reported for the bacterial species Lactobacillus plantarum. To study in vivo human responses to L. plantarum, a randomised double-blind placebo-controlled cross-over study was performed. Healthy adults were provided preparations of living and heat-killed L. plantarum bacteria, biopsies were taken from the intestinal mucosa and altered transcriptional profiles were analysed. Transcriptional profiles of human epithelia displayed striking differences upon exposure to living L. plantarum bacteria harvested at different growth phases. Modulation of NF-?B-dependent pathways was central among the major altered cellular responses. This unique in vivo study shows which cellular pathways are associated with the induction of immune tolerance in mucosal tissues towards common adjuvanticity possessing lactobacilli. Keywords: mucosal response of healthy adult humans to lactic acid bacteria Overall design: This study was set up according to a randomised double-blind cross-over placebo-controlled design. It contains transcriptional profiles from biopsies from 8 healthy individuals after oral intake of three different growth stages of Lactobacillus plantarum or placebo control. In total, this study includes data from 8 individuals x 4 treatments=32 arrays.

Project description:Probiotic bacteria, specific representatives of bacterial species that are a common part of the human microbiota, are proposed to deliver health benefits to the consumer by modulation of intestinal function via largely unknown molecular mechanisms. To explore in vivo mucosal responses of healthy adults to probiotics, we obtained transcriptomes in an intervention study following a double-blind placebo-controlled cross-over design. In the mucosa of the proximal small intestine of healthy volunteers, probiotic strains from the species Lactobacillus acidophilus, L. casei and L. rhamnosus each induced differential gene regulatory networks and pathways in the human mucosa. Comprehensive analyses revealed that these transcriptional networks regulate major basal mucosal processes, and uncovered remarkable similarity to response profiles obtained for specific bioactive molecules and drugs. This study elucidates how intestinal mucosa of healthy humans perceive different probiotics and provides avenues for rationally designed tests of clinical applications. Keywords: mucosal response of healthy adult humans to lactic acid bacteria Overall design: This study was set up according to a randomised double-blind cross-over placebo-controlled design. It contains transcriptional profiles from biopsies from 7 healthy individuals after oral intake of three different Lactobacillus species or placebo control. In total, this study includes data from 7 individuals x 4 treatments=28 arrays.

Project description:Probiotic bacteria, specific representatives of bacterial species that are a common part of the human microbiota, are proposed to deliver health benefits to the consumer by modulation of intestinal function via largely unknown molecular mechanisms. To explore in vivo mucosal responses of healthy adults to probiotics, we obtained transcriptomes in an intervention study following a double-blind placebo-controlled cross-over design. In the mucosa of the proximal small intestine of healthy volunteers, probiotic strains from the species Lactobacillus acidophilus, L. casei and L. rhamnosus each induced differential gene regulatory networks and pathways in the human mucosa. Comprehensive analyses revealed that these transcriptional networks regulate major basal mucosal processes, and uncovered remarkable similarity to response profiles obtained for specific bioactive molecules and drugs. This study elucidates how intestinal mucosa of healthy humans perceive different probiotics and provides avenues for rationally designed tests of clinical applications. Keywords: mucosal response of healthy adult humans to lactic acid bacteria This study was set up according to a randomised double-blind cross-over placebo-controlled design. It contains transcriptional profiles from biopsies from 7 healthy individuals after oral intake of three different Lactobacillus species or placebo control. In total, this study includes data from 7 individuals x 4 treatments=28 arrays.

Project description:The aim of this study was to investigate the effects of three Lactobacillus plantarum strains on in-vivo small intestinal barrier function and gene transcription in human subjects. The strains were selected for their differential effects on TLR signalling and tight junction protein rearrangement, which may lead to beneficial effects in a stressed human gut mucosa. Ten healthy volunteers participated in four different intervention periods: 7-day oral intake of either L. plantarum WCFS1, CIP48 (CIP104448), TIFN101 (CIP104450) or placebo, proceeded by a 4 weeks wash-out period. Lactulose-rhamnose ratio (an indicator of small intestinal permeability) increased after intake of indomethacin, which was given as an artificial stressor of the gut mucosal barrier (mean ratio 0.06±0.04 to 0.10±0.06, p=0.001), but was not significantly affected by the bacterial interventions. However, gene transcription pathway analysis in small intestinal biopsies, obtained by gastroduodenoscopy, demonstrated that particularly L. plantarum TIFN101 modulated cell-cell adhesion with high turnover of genes involved in tight- and adhesion junction protein synthesis and degradation (e.g. actinin alpha-4, metalloproteinase-2). These effects were less pronounced for L. plantarum WCFS1 and CIP104448. In conclusion, L. plantarum TIFN101 induced the most pronounced probiotic properties with specific effects on repair processes in the compromised intestine of healthy subjects. Overall design: Ten healthy volunteers participated in a randomized double-blind placebo-controlled cross-over trial in which four different interventions were evaluated: 7-day oral intake of either L. plantarum WCFS1, CIP48 (CIP104448), TIFN101 (CIP104450), or placebo; after which mucosal biopsies from the duodenum were obtained for gene expression profiling.

Project description:The effects of a 2-week suppletion period with L. plantarum WCFS1 on duodenal gene expression profiles was investigated in healthy subjects in a placebo-controlled doouble-blind study. Each subject ingested a supplement containing L. Plantarum WCFS1 once a day. After that period, tissue samples from the horizontal part of the duodenum were obtained by standard flexible gastroduodenoscopy, and Affymetrix microarrays were used to determine genome-wide gene expression profiles.

Project description:The effects of a 2-week suppletion period with L. plantarum WCFS1 on duodenal gene expression profiles was investigated in healthy subjects in a placebo-controlled doouble-blind study. Each subject ingested a supplement containing L. Plantarum WCFS1 once a day. After that period, tissue samples from the horizontal part of the duodenum were obtained by standard flexible gastroduodenoscopy, and Affymetrix microarrays were used to determine genome-wide gene expression profiles.

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